Biomedical subjects

A Feigenbaum

Publications and source records attributed to A Feigenbaum.

At least 19 recordsLinked to original sources

PubMed2006

A study on the nature of genetic metabolic practice at a major paediatric referral centre.

A retrospective chart review of new paediatric patients seen during the calendar year 1998 by specialists of the Division of Clinical and Metabolic Genetics of the Hospital for Sick Children in Toronto, the largest such referral centre in the country, showed that 81% of specific genetic metabolic diagnoses were made within one month of being seen in consultation by one of the consultants of the programme. In 5% of cases, a specific diagnosis was not reached 4 years after initial consultation. We concluded from this study that the specific diagnosis of inborn errors of metabolism at a major medical genetic referral centre tended to be made quickly, or never. Some of the causes of delays in diagnosis include (1) the lack of ready access to existing diagnostic laboratory testing; (2) technical barriers to the identification of specific metabolic or genetic defects; and (3) incomplete knowledge of genetic defects causing inherited metabolic diseases.

Adolescent↗

PubMed2006

Atypical phenotype in a boy with a maple syrup urine disease.

Maple syrup urine disease (MSUD) is a metabolic disorder due to a block in the decarboxylation step in the catabolic pathways of the branched-chain amino acids (BCAAs). We describe an atypical presentation in an infant male. The patient presented with psychomotor retardation, profound hypotonia and elevated plasma levels of BCAAs, but no elevation of alloisoleucine. Cranial magnetic resonance imaging showed prominent diffuse CSF spaces, delayed myelin maturation and symmetrical signal abnormality within the globi pallidi, midbrain, dorsal pons and medulla. The cerebellar white matter was specifically spared. A mitochondrial disorder was suggested. After correction of feeding problems with G-tube feeds, his high BCAAs persisted and, on fourth analysis, alloisoleucine was seen. Subsequent fibroblast enzyme and mutation analysis confirmed MSUD due to E(1)-alpha subunit deficiency. After starting dietary treatment, there was no significant improvement in his hypotonia or his psychomotor development. However, the high signal within the globi pallidi had resolved. MSUD may have diverse clinical presentations, and should be considered in children who present with chronic psychomotor delay but no acute encephalopathic episodes. BCAA levels may not be very high, alloisoleucine may not always be detected in MSUD even with severe enzyme deficiency, and imaging may be misleading if seen in the chronic phase only.

Amino Acids, Branched-Chain↗

PubMed2006

Modelling of migration from multi-layers and functional barriers: estimation of parameters.

Functional barriers form parts of multi-layer packaging materials, which are deemed to protect the food from migration of a broad range of contaminants, e.g. those associated with reused packaging. Often, neither the presence nor the identity of the contaminants is known, so that safety assessment of the materials has to rely on predictive tools. Several complementary freeware described here allow one to model diffusion in multi-layer films. These tools require the input of parameters that are not easy to determine or predict. Previous work has focused on the prediction of diffusion coefficients at storage temperatures of packaging in contact with food. However, many other kinetic and thermodynamic parameters are needed to describe transport properties during the processing of a material at high temperature and during its shelf-life. All parameters needed for the calculations are discussed. In order to propose default values, the approach consists of (1) reviewing the available literature data, (2) running experiments on polypropylene, polyethylene and poly(ethylene vinyl alcohol) in typical conditions (separately diffusion during processing and migration) and (3) simulating numerical sets for typical situations. Several freeware are proposed to simulate migration from multi-layers and functional barriers using the default parameters.

Computer Simulation↗

PubMed2005

Evaluation of migration models that might be used in support of regulations for food-contact plastics.

Materials and articles intended to come into contact with food must be shown to be safe because they might interact with food during processing, storage and the transportation of foodstuffs. Framework Directive 89/109/EEC and its related specific Directives provide this safety basis for the protection of the consumer against inadmissible chemical contamination from food-contact materials. Recently, the European Commission charged an international group of experts to demonstrate that migration modelling can be regarded as a valid and reliable tool to calculate 'reasonable worst-case' migration rates from the most important food-contact plastics into the European Union official food simulants. The paper summarizes the main steps followed to build up and validate a migration estimation model that can be used, for a series of plastic food-contact materials and migrants, for regulatory purposes. Analytical solutions of the diffusion equation in conjunction with an 'upper limit' equation for the migrant diffusion coefficient, D(P), and the use of 'worst case' partitioning coefficients K(P,F) were used in the migration model. The results obtained were then validated, at a confidence level of 95%, by comparison with the available experimental evidence. The successful accomplishment of the goals of this project is reflected by the fact that in Directive 2002/72/EC, the European Commission included the mathematical modelling as an alternative tool to determine migration rates for compliance purposes.

Diffusion↗

PubMed2005

Functional barriers: properties and evaluation.

Functional barriers are multilayer structures deemed to prevent migration of some chemicals released by food-contact materials into food. In the area of plastics packaging, different migration behaviours of mono- and multilayer structures are assessed in terms of lag time and of their influence of the solubility of the migrants in food simulants. Whereas barriers to oxygen or to aromas must prevent the diffusion of these compounds under conditions of use, a functional barrier must also be efficient under processing conditions, to prevent diffusion of substances when the polymer layers are in contact at high (processing) temperatures. Diffusion in melted polymers at high temperatures is much slower for glassy polymers, than in polymers that are rubbery at ambient temperature. To evaluate the behaviour of functional barriers under conditions of use, a set of reference diffusion coefficients in the 40-60 degrees C range were determined for 14 polymers. Conditions for accelerated migration tests are proposed based on worst-case activation energy in the 40-60 degrees C range. For simulation of migration, numerical models are available. The rules derived from the models can be used both by industry (to optimize a material in terms of migration) or by risk assessors. Differences in migration behaviour between mono- and multilayer materials are discussed.

Alkanes↗

PubMed2003

Mechanism of migration from agglomerated cork stoppers. Part 2: Safety assessment criteria of agglomerated cork stoppers for champagne wine cork producers, for users and for control laboratories.

Producers of cork for champagne and wine have to be certain the corks meet the requirements of the European Union Framework Directive, and comply with the evaluations of chemicals carried out in the European Union. To identify chemicals in cork with the potential to migrate, the different synthetic products on the market were classified based on their technical role and of the chemistry involved. The potential migrants in each class (adhesive for cork bodies, adhesive for cork disks, lubricants and surface treatments) were analysed spectroscopically and chromatographically. A general approach was proposed for the evaluation of each commercial chemical: the detailed composition was supplied and verified mainly by infrared spectroscopy, proton nuclear magnetic resonance spectroscopy ((1)H-NMR) and GC-MS. A procedure to determine primary aromatic amines, specifically for cork migrates, based on GC-MS was developed. These techniques focussed on migrants below 1000 g mol(-1), as higher molecular weight chemicals are not likely to pose a problem for public health. The products were also tested after polymerization. The analytical scheme included an analytical check of synthetic product formulation and identification of potential migrants, solvent extraction and analysis of cork extracts.

Adhesives↗

PubMed2002

Migration of additives from polymers into food simulants: numerical solution of a mathematical model taking into account food and polymer interactions.

The principle of a computing program describing precisely the migration of additives from a polymer into a food simulant is presented. As six parameters are used to fit the simulnnt sorption and additive extraction kinetics, the parameters have been determined by independent experiments. Owing to the complicated coupling between the liquid and additive diffusion processes, migration kinetics cannot be obtained by a mathematical resolution of kinetic equations, but they must be calculated by numerical analysis. The method is applied to a UV absorber in polypropylene migrating into glyceryl tripelargonate, a pure triglyceride, of which behaviour and average molecular weight are similar to official fatty food simulants. Properly designed experiments validate the model used to fit the migration kinetics. The possibility of erasing any parameters is also discussed.

Computer Simulation↗

PubMed2002

Safety and quality of food contact materials. Part 1: evaluation of analytical strategies to introduce migration testing into good manufacturing practice.

The results of a research project (EU AIR Research Programme CT94-1025) aimed to introduce control of migration into good manufacturing practice and into enforcement work are reported. Representative polymer classes were defined on the basis of chemical structure, technological function, migration behaviour and market share. These classes were characterized by analytical methods. Analytical techniques were investigated for identification of potential migrants. High-temperature gas chromatography was shown to be a powerful method and 1H-magnetic resonance provided a convenient fingerprint of plastic materials. Volatile compounds were characterized by headspace techniques, where it was shown to be essential to differentiate volatile compounds desorbed from those generated during the thermal desorption itself. For metal trace analysis, microwave mineralization followed by atomic absorption was employed. These different techniques were introduced into a systematic testing scheme that is envisaged as being suitable both for industrial control and for enforcement laboratories. Guidelines will be proposed in the second part of this paper.

Chromatography, Gas↗

PubMed2002

Integrated approach of migration prediction using numerical modelling associated to experimental determination of key parameters.

The principle of utilizing a computing program describing precisely the migration of additives from a polymer into a food simulant is presented. The model has been validated with a UV absorber in polypropylene migrating into glyceryl tripelargonate, a pure triglyceride whose behaviour and average molecular weight are similar to Myglyol (a synthetic mixture of C8-C12 triglycerides). Six parameters were used to fit the simulant sorption and additive extraction kinetics, and these were determined by independent experiments. The possibility of eliminating any of the parameters is also discussed. This work provides the first consistent set of experimental data that can be used to overestimate the diffusion coefficients of additives both in virgin (without contact with solvent) and in swollen (fat contact) polymer. The influence of mobility increase brought out by temperature or swelling are compared. The effects were more important for high molecular weight compounds.

Diffusion↗

PubMed2002

Tailoring fatty food simulants made from solvent mixtures (2): determining the equivalent migration behaviour of olive oil and of solvents in the case of polyolefins.

It is suggested that solvent mixtures consisting of an ester and of an inert solvent can be used as fatty food simulants capable of having the same migration behaviour as olive oil with plastics. Migration tests carried out with low-density polyethylene for 20 and 48 h in an 8 and 5% mixture of tert-butyl acetate in ethanol respectively gave results equivalent to those obtained with olive oil after 10 days at 40 degrees C. The use of solvent mixtures facilitated the analysis and improved detection limits, giving good repeatability. Furthermore, the more rapid migration in solvent mixtures can be particularly useful for industrial controls as alternative test methods.

Diffusion↗

PubMed2001

A novel syndrome affecting multiple mitochondrial functions, located by microcell-mediated transfer to chromosome 2p14-2p13.

We have studied cultured skin fibroblasts from three siblings and one unrelated individual, all of whom had fatal mitochondrial disease manifesting soon after birth. After incubation with 1 mM glucose, these four cell strains exhibited lactate/pyruvate ratios that were six times greater than those of controls. On further analysis, enzymatic activities of the pyruvate dehydrogenase complex, the 2-oxoglutarate dehydrogenase complex, NADH cytochrome c reductase, succinate dehydrogenase, and succinate cytochrome c reductase were severely deficient. In two of the siblings the enzymatic activity of cytochrome oxidase was mildly decreased (by approximately 50%). Metabolite analysis performed on urine samples taken from these patients revealed high levels of glycine, leucine, valine, and isoleucine, indicating abnormalities of both the glycine-cleavage system and branched-chain alpha-ketoacid dehydrogenase. In contrast, the activities of fibroblast pyruvate carboxylase, mitochondrial aconitase, and citrate synthase were normal. Immunoblot analysis of selected complex III subunits (core 1, cyt c(1), and iron-sulfur protein) and of the pyruvate dehydrogenase complex subunits revealed no visible changes in the levels of all examined proteins, decreasing the possibility that an import and/or assembly factor is involved. To elucidate the underlying molecular defect, analysis of microcell-mediated chromosome-fusion was performed between the present study's fibroblasts (recipients) and a panel of A9 mouse:human hybrids (donors) developed by Cuthbert et al. (1995). Complementation was observed between the recipient cells from both families and the mouse:human hybrid clone carrying human chromosome 2. These results indicate that the underlying defect in our patients is under the control of a nuclear gene, the locus of which is on chromosome 2. A 5-cM interval has been identified as potentially containing the critical region for the unknown gene. This interval maps to region 2p14-2p13.

Amino Acids↗

PubMed2001

Influence of packaging on the aroma stability of strawberry syrup during shelf life.

Different types of packaging (glass bottle, PVC, and PET) were compared for the preservation of aroma quality of a strawberry syrup during shelf life. Esters, alcohols, and aldehydes were analyzed by solid-phase micro-extraction (SPME) and solvent extraction. During storage, hydrolysis of esters in acids and alcohols led to a modification of the aroma profile which can be explained by the replacement of "fruity" and "fresh" notes by "dairy note" in the syrup. Aroma compounds that are responsible for fruity notes, such as methyl cinnamate, methyl anthranilate, and methyl dihydrojasmonate, were strongly reduced after 90 days. This could be explained by a selective interaction of these compounds with the polymer matrix (PET or PVC). After 330 days, a later and important decrease of the "fruity notes" occurred in both PETs; so PVC2 and the glass bottle were found to be able to maintain a balanced aroma for long-term storage.

Alcohols↗

PubMed2001

Tailoring fatty food simulants made from solvent mixtures (1): comparison of methanol, ethanol and isopropanol behaviour with polystyrene.

To investigate the use of solvent mixtures as test media replacing olive oil in migration tests, the interaction of polystyrene with mixtures composed of various amounts of tert.butyl acetate (mimicking the ester functions of oil) and of a low molecular weight alcohol (methanol, ethanol and isopropanol as inert co-solvent) was studied, using FTIR. Isopropanol, which has a lesser tendency to form hydrogen bonds in the plastic, can be used as main component of alternative fatty test media, its aggressiveness to polystyrene being tailored by adjusting the concentration of tert.butyl acetate. Concentrations below 20% seem useful on the basis of the mechanism of displacement of the alcohols.

2-Propanol↗

PubMed2000

Neuropsychological function in mild hyperphenylalaninemia.

Whether specific cognitive deficits related to frontal-lobe dysfunction that have been reported in individuals with phenylketonuria (PKU) are also characteristic of mild hyperphenylalaninemia (MHP) was investigated. Tests of executive function and control tasks not assessing executive function were administered to a group of individuals with MHP and a group without MHP, similar in age, gender, and IQ. Tests of academic skills and behavior-rating questionnaires were also administered to the group with MHP. No group differences were found for any measure, suggesting that the mild elevations of phenylalanine in individuals with MHP are not sufficient to produce behavioral and cognitive impairments characteristic of PKU.

Adolescent↗

PubMed1999

Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews.

We studied 13 patients with lipoamide dehydrogenase (LAD) deficiency, originating from seven Ashkenazi Jewish families. Their disease was characterized by recurrent attacks of vomiting, abdominal pain, and encephalopathy accompanied by elevated liver transaminases, prolonged prothrombin time, and occasionally associated with lactic and ketoacidemia or with myoglobinuria. Two patients who presented neonatally suffered from residual neurological damage with attention deficit hyperactive disorder, mild ataxia, motor incoordination, muscle hypotonia, and weakness. Nine patients who presented in early childhood or later suffered from exertional fatigue between decompensation episodes but were otherwise asymptomatic. Two patients died because of intractable metabolic acidosis and multi-organ failure. In all patients LAD activity was reduced to 8 to 21% of the control in muscle or lymphocytes. In four patients LAD protein in muscle was reduced to 20 to 60% of the control. Direct sequencing of the cDNA of the LAD gene showed that 12 of the 14 mutated alleles carried the G229C mutation and two carried an insertion mutation 105insA (Y35X). The patients who presented neonatally and had more severe sequelae were compound heterozygotes for the two mutations; patients who presented in early childhood or later were homozygous for the G229C mutation. Using an allele-specific oligonucleotide hybridization technique, nine heterozygotes for the G229C mutation were identified among 845 anonymous individuals of Ashkenazi Jewish origin disclosing a carrier rate of 1:94. Because of the significant morbidity associated with the disease, screening for the G229C mutation among Ashkenazi Jewish couples should be considered.

Adult↗

PubMed1999

Prediction of worst case migration: presentation of a rigorous methodology.

An improvement of the Piringer model, allowing the prediction of a worst case migration from packaging to food is presented here. The authors are proposing other constants for the calculation of the upperbound value of the diffusion coefficient, using experimental data determined by a film to film method. Considering the plasticizing effects of food simulants, a model involving the variation of the diffusion coefficient versus space and time must be used. Future fields of investigation are discussed: the relationship between diffusion coefficients and the volume of the migrant (instead of molar mass), and the variation of diffusion coefficient activation energy with temperature.

Computer Simulation↗

PubMed1998

Human sulfite oxidase R160Q: identification of the mutation in a sulfite oxidase-deficient patient and expression and characterization of the mutant enzyme.

Sulfite oxidase catalyzes the terminal reaction in the degradation of sulfur amino acids. Genetic deficiency of sulfite oxidase results in neurological abnormalities and often leads to death at an early age. The mutation in the sulfite oxidase gene responsible for sulfite oxidase deficiency in a 5-year-old girl was identified by sequence analysis of cDNA obtained from fibroblast mRNA to be a guanine to adenine transition at nucleotide 479 resulting in the amino acid substitution of Arg-160 to Gln. Recombinant protein containing the R160Q mutation was expressed in Escherichia coli, purified, and characterized. The mutant protein contained its full complement of molybdenum and heme, but exhibited 2% of native activity under standard assay conditions. Absorption spectroscopy of the isolated molybdenum domains of native sulfite oxidase and of the R160Q mutant showed significant differences in the 480- and 350-nm absorption bands, suggestive of altered geometry at the molybdenum center. Kinetic analysis of the R160Q protein showed an increase in Km for sulfite combined with a decrease in kcat resulting in a decrease of nearly 1,000-fold in the apparent second-order rate constant kcat/Km. Kinetic parameters for the in vitro generated R160K mutant were found to be intermediate in value between those of the native protein and the R160Q mutant. Native sulfite oxidase was rapidly inactivated by phenylglyoxal, yielding a modified protein with kinetic parameters mimicking those of the R160Q mutant. It is proposed that Arg-160 attracts the anionic substrate sulfite to the binding site near the molybdenum.

Child, Preschool↗

PubMed1998

Alternative test methods to control the compliance of polyolefin food packaging materials with the European Union regulation: the case of aromatic antioxidants and of bis(ethanolamine) antistatics based on 1H-NMR and UV-visible spectrophotometry.

In order to decide whether a plastic food packaging material complies with the European Communities (EC) regulation on migration, a quick analysis of two functional classes of plastics additives (aromatic antioxidants and antistatic agents) from polyolefin materials by 1H-NMR and UV-visible spectrophotometry is presented. The scope of spectroscopic methods for alternative and migration tests is presented. 1H-NMR can be used in several ways, from a simple fingerprint of the potential migrants to an identification procedure. Extraction is optimized using UV spectrophotometry. Optimization relies on extraction kinetics, which include the demonstration that extraction is more severe than migration. Only a few hours are required to conclude whether a material complies with the regulation. The specific migration limits are expressed as specific absorbance limit values, alpha. These data can be annexed by food industries to specifications of a plastic packaging material.

Antioxidants↗